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FLASH GENE
Symbol CCL2 contributors: mct/ - updated : 27-01-2015
HGNC name chemokine (C-C motif) ligand 2
HGNC id 10618
Location 17q12      Physical location : 32.582.295 - 32.584.218
Synonym name
  • small inducible cytokine A2
  • monocyte chemoattractant protein-1
  • monocyte chemotactic and activating factor
  • monocyte secretory protein JE
  • small inducible cytokine subfamily A (Cys-Cys), member 2
  • Synonym symbol(s) MCAF, MCP1, MCP-1, SCYA2, GDCF-2, SMC-CF, GDCF-2, HC11, MGC9434, HSMCR30
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 1.93 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    SPACA3 17q12 sperm acrosome associated 3 ACCN1 17q11.2-q12 amiloride-sensitive cation channel 1, neuronal (degenerin) LOC339212 17q12 similar to tousled-like kinase 2; serine/threonine kinase; tousled-like kinase CCL2 17q11.2-q21.1 chemokine (C-C motif) ligand 2 CCL7 17q11.2-q12 chemokine (C-C motif) ligand 7 CCL11 17q21.1-q21.2 chemokine (C-C motif) ligand 11 CCL8 17q11.2 chemokine (C-C motif) ligand 8 CCL13 17q11.2 chemokine (C-C motif) ligand 13 CCL1 17q11.2 chemokine (C-C motif) ligand 1 LOC124842 17q12 hypothetical protein LOC124842 CCT6B 17q11.2 chaperonin containing TCP1, subunit 6B (zeta 2) MGC20398 17q21.1 hypothetical protein MGC20398 LIG3 17q11.2-q12 ligase III, DNA, ATP-dependent LOC117584 17q21.1 fring RAD51L3 17q11 RAD51-like 3 (S. cerevisiae) DKFZp434H2215 17q21.1 hypothetical protein DKFZp434H2215 FLJ10458 17q21.1 Notchless gene homolog (Drosophila) CMYA4 17q21.1 cardiomyopathy associated 4 FLJ40154 17q21.1 hypothetical protein FLJ40154 MGC19764 17q21.1 hypothetical protein MGC19764 FLJ34922 17q21.1 hypothetical protein FLJ34922 FLJ10260 17q21.1 hypothetical protein FLJ10260 FLJ31952 17q21.1 hypothetical protein FLJ31952 LOC342615 17q21.1 similar to Adenylosuccinate synthetase 2 (IMP--aspartate ligase 2) (AdSS 2) (AMPSase 2)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 760 10.9 99 - 1998 9558113
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestiveintestinelarge intestinecolon moderately
     pharynx   highly
    Endocrinepancreas   highly
    Nervousspinal cordposterior horn  highly Mus musculusAdult
    Respiratorylung   moderately
    Urinarykidney   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    Connectivebone  moderately
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    Nervousastrocyte Mus musculusAdult
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies homolog to murine Ccl2 (67.37 pc)
    intraspecies homolog to SCYA7
    Homologene
    FAMILY
  • CXC subfamily of cytokines
  • intercrine beta (chemokine CC) family
  • CATEGORY immunity/defense , signaling cytokine , receptor membrane G
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • chemotactic factor for monocytes and basophils
  • induces proliferation and interleukin-6 production in smooth muscle cells by differential activation of nuclear factor-kappa B and activator protein-1
  • playing an important role in attracting monocytes to sites of inflammation, and in the recruitment and activation of monocytes during inflammation
  • acting as a paracrine and autocrine factor for growth and invasion in prostate cancer
  • a key molecule involved in the regulation of monocyte/macrophage immigration and activation, and therefore is involved in a broad variety of neurological and non-neurological diseases
  • mediates fibroblast survival by inhibiting apoptosis through IL-6/STAT3 signaling and may contribute to the development and maintenance of lung fibrosis
  • contributes to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes
  • plays a critical role in the recruitment and activation of leukocytes and implicated in the regulation of osteoclast cell-cell fusion
  • regulating osteoclastogenesis in an autocrine/paracrine manner under the stimulation of TNFSF11 in osteoclasts
  • plays a critical role in the development of heart failure that is known to involve apoptosis
  • causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing ZC3H12A
  • important mediator of macrophage-related neural damage in models of two distinct inherited neuropathies
  • enhances efferocytosis through RAC1 activation
  • with its receptor CCR2 may contribute to neuropathic pain development
  • has the typical characteristics of a neuronal mediator involved in nociceptive signal processing
  • association of CCL2 with OLR1 and LPA may play a role in modulating monocyte trafficking during atherogenesis
  • one of the vital chemokines that control the migration and infiltration of monocytes/macrophages
  • obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis
  • major role as a chemoattractant of monocytes for immunological surveillance and to site of inflammation
  • mediates anti-fibrotic effects independently of CCR2 in human fibroblasts of different origins
  • regulates macrophage cytotoxicity in abdominal aortic aneurysm
  • CCL2-mediated skeletal muscle macrophages recruitment plays likely a role in the etiology of Type 2 Diabetes
  • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling signal transduction
  • CCL2/RAC1/PI3K pathway plays critical role in resolution of acute lung inflammation
  • CCL2-CCR2 signaling may be involved in the maintenance of orofacial neuropathic pain via astroglial-neuronal interactio
  • plays a key role in monocyte/macrophage recruitment and in macrophage-dependent inflammatory responses that lead to the development of atherosclerosis and insulin resistance
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • triggering JAK2 activation and tyrosine phosphorylation of CCR2-B
  • binds to chemokine receptors CCR2 and CCR4
  • interacting with PRKCB1 for the chemotactic response of monocytes to CCL2
  • CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the ACKR2 decoy chemokine receptor
  • PIK3CG is essential for CCL2-stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving CCL2 secretion and CCR2 activation
  • CCL2/CCR2 (interaction is responsible for the infiltration of peripheral cells to the thymus in the Th1-inflammatory/infectious situations
  • HDAC2 may act as a negative regulator of CCL2
  • TWIST1 expression did not increase the secretion of the common proangiogenic factors VEGFA and basic fibroblast growth factor but rather induced expression of the macrophage chemoattractant CCL2
  • osteoblast and osteocyte CCL2 expression is an important mediator for the anabolic effects of PTH on bone 4)
  • NFKBIZ is directly recruited to the proximal promoter region of the CCL2 gene and is required for transcription-enhancing histone H3 at lysine-4 trimethylation
  • OLR1 binds CCL2 and the OLR1-bound CCL2 retains its ability to recruit monocytes
  • CCL2 and CCR2 have been shown to be induced and involved in various neurodegenerative disorders including Alzheimer disease, multiple sclerosis, and ischemic brain injury
  • ZXDC is a regulator in the process of myeloid function and is responsible for CCL2 gene de-repression by BCL6
  • OLR1 promotes migration and adhesion of bone marrow-derived mesenchymal stem cells via regulation of CCL2 expression
  • NR1D1 regulates the inflammatory infiltration of macrophages through the suppression of CCL2 expression
  • CCL2 modulate macrophage cytotoxicity by increasing the level of membrane bound FASLG
  • FLI1 gene actively promotes transcription from the CCL2 gene promoter in a dose-dependent manner
  • overexpression of TERF1 in aging endothelial cells (EC) reduced telomere-associated DNA damage foci and reduced expression levels of CCL2
  • TICAM1 regulated foam cell formation via regulation of the expression levels of CCL2, F3, OLR1
  • cell & other
    REGULATION
    induced by DLL4, inducing CCL2 expression in arteries and adipose tissues
    repressed by inhibitors selective for the subset of serine/threonine kinases, protein kinase C (PKC)
    Other upregulated by inflammatory mediators (IL-1alpha & TNF-alpha) and downregulated by hypoxia in cardiac cells
    EDN1 induces mRNA and protein secretion of CCL2 and IL6, forming an autocrine signaling pathway that stimulates collagen accumulation in the extracellular matrix
    specifically regulated during activation of skeletal repair and remodeling (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in chronic hepatite C virus infection and in amyotrophic lateral sclerosis progressing most rapidly
    constitutional     --over  
    associated with chronic inflammation may contribute to the development of heart failure
    tumoral     --over  
    clinical association of CCL2 overexpression in human cancers with poor prognosis
    tumoral     --over  
    CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer
    Susceptibility
  • to severe chronic hepatite C virus infection (HCV)
  • to pulmonary tuberculosis
  • to idiopathic dilated cardiomyopathy (IDC)
  • Variant & Polymorphism other
  • associated with the susceptibility to RA
  • 2518 CCL2 G allele, may predispose HCV patients to more severe hepatic inflammation and fibrosis, and predisposing to severe pulmonary tuberculosis
  • G allele at -2518 may be a novel genetic marker of susceptibility to nonfamilial IDC
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularneuropathy 
    attenuation of CCL2 upregulation by inhibition of ERK phosphorylation appears to be a most promising approach to treat a broader spectrum of inherited peripheral neuropathies
    diabete  
    use of therapeutic strategies aimed at antagonizing CCL2 or IL6 signaling in diabetic kidney injury
    miscelleaneouspain 
    antagonists of CCL2/CCR2 are promising agents from treating neuropathic pain.
    miscelleaneouspain 
    targeting CCL2-CCR2 signaling may be a potentially important new treatment strategy for trigeminal neuralgia
    ANIMAL & CELL MODELS
  • Mcp1 -/- mice synthesized extremely low levels of interleukin-4, interleukin-5, and interleukin-10
  • in Gjb1-deficient mice (Cx32def), Ccl2 is upregulated in a MEK–ERK-dependent manner (CCL2 reduction is a promising strategy to treat CMT1 neuropathies, particularly in disease forms where axon damage is predominant as in Cx32def mice and the corresponding human disorder, CMT1X)
  • macrophages from Ccr2-null mice were not capable of promoting trans-endothelial migration of tumour cells